The objective of this research project is an understanding of the structural basis for important biological differences in the subspecies of two different immunoregulatory proteins: 1) The two phytohemagglutinin (PHA) lectin subunits, only one of which is a mitogen, have significantly different biological properties in spite of evidence of extensive structural homology. 2) Human alpha-fetoprotein (HAFP) subfractions have widely differing immunosuppressive potencies that correlate with molecular microheterogeneity as detected by several techniques. Structure-function relations in these two systems will be studied by the following means: 1) Complete amino acid and oligosaccharide sequencing of the two PHA subunits will be performed by well-described methods, and their structures will be contrasted as well as compared with different lectins studied by others. 2) Limited modifications of the amino acid residues and the oligosaccharide moieties of the PHA subunits will be tested for their effects on biological activities. 3) HAFP subfractions purified by means of ion exchange chromatography, will be studied structurally by the sequencing of selected cyanogen bromide fragments and by studies on possible phosphoserine in some HAFP subspecies. 4) Sequential glycosidase treatment of the HAFP oligosaccharide will also be tested for its effects on HAFP immunosuppressive potency. The results of these studies will contribute to the understanding of the structural basis of the function of soluble mediators of cellular immune function acting through signals carried by way of lymphocyte surface receptors. Ultimately, this knowledge will be applied to studies of the mechanisms of the control of growth and differentiation in normal and in neoplastic cells by cell surface events.